Mitochondrial targeting of the p13 super(II) protein coded by the X-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I)

• Published in: Oncogene Vol. 18; no. 31; pp. 4505 - 4514
• Main Authors: Ciminale, V, Zotti, L, D'Agostino, D M, Ferro, T, Casareto, L, Franchini, G, Bernardi, P, Chieco-Bianchi, L
• Format: Journal Article
• Language: English
• Published: 05.08.1999
• Subjects: Human T-lymphotropic virus 1
• ISSN: 0950-9232

The X region of the HTLV-I genome contains four major open reading frames (ORFs), two of which, termed x-I and x-II, are of still undefined biological significance. By indirect immunofluorescence and dual labeling with marker proteins, we demonstrate that p13 super(II), an 87-amino acid protein coded by the x-II ORF, is selectively targeted to mitochondria. Mutational analysis revealed that mitochondrial targeting of p13 super(II) is directed by an atypical 10-amino acid signal sequence that is not cleaved upon import and is able to target the Green Fluorescent Protein to mitochondria. Expression of p13 super(II) results in specific alterations of mitochondrial morphology and distribution from a typical string-like, dispersed network to round-shaped clusters, suggesting that p13 super(II) might interfere with processes relying on an intact mitochondrial architecture. Functional studies of mitochondria with the cationic fluorochrome tetramethylrhodamine revealed that a subpopulation of the cells with p13 super(II)-positive mitochondria show a disruption in the mitochondrial inner membrane potential ( Delta psi ), an early event observed in cells committed to apoptosis. Taken together, these results suggest novel virus-cell interactions that might be important in HTLV-I replication and/or pathogenicity.